A future for antigenspecific immunotherapy for multiple sclerosis
ECTRIMS Online Library. Wraith D. 09/13/19; 279539; 277
David Wraith
David Wraith
Contributions
Abstract

Abstract: 277

Type: Scientific Session

Abstract Category: Scientific Session 12: Immunopathogenesis and antigen-specific thera

D. Wraith1, J. Chataway2, ATX-MS1467 Study Group

1Immunology & Immunotherapy | Medical & Dental Sciences, University of Birmingham, Birmingham, 2University College London (UCL) Institute of Neurology, London, United Kingdom

Autoimmune conditions can be treated by tolerance induction with peptide epitopes; this presentation will focus on the mechanisms involved and results from clinical trials of antigen-specific immunotherapy in multiple sclerosis. Peptides are designed as antigen processing independent epitopes (Apitopes) that mimic naturally processed antigens. Apitope induced peripheral tolerance is characterised by the generation of anergic, IL-10 secreting CD4+ T-cells with regulatory function. Clinical trials have tested the tolerability and efficacy of the peptide cocktail ATX-MS-1467 in participants with relapsing multiple sclerosis (RMS). Study 1 was a multicentre Phase 1b safety evaluation comparing intradermal (i.d., Cohort 1) with subcutaneous (Cohort 2) administration in 43 participants. Both cohorts received ATX-MS-1467 dosed at 25, 50, 100, 400, and 800 µg at 14-day intervals over 8 weeks, followed by 8 weeks with 4 additional 800 µg doses at 14-day intervals and 32 weeks off study medication. Study 2 was a Phase 2a, multicentre, single-arm, trial enrolling 37 participants. ATX-MS-1467 was titrated from 50 µg i.d. on Day 1 to 200 µg on Day 15 and 800 µg on Day 29 followed by biweekly administration of 800 µg for 16 weeks and 16 weeks off study medication. Efficacy was evaluated on MRI parameters and clinical variables. Safety end points included treatment-emergent adverse events and injection-site reactions. In Study 1 there was a significant decrease in new/persisting T1 GdE lesions in Cohort 1 from baseline to Week 16, returning to baseline values at week 48. In Study 2, the number of T1 GdE lesions were significantly reduced on treatment and remained reduced at study completion. Safety results were unremarkable in both studies. Based on these results we conclude that relatively slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions and a sustained effect post-treatment.
Disclosure: DW serves as Chief Scientific Officer for Apitope Technology (Bristol) Ltd and Apitope International NV on a consultative basis.

Abstract: 277

Type: Scientific Session

Abstract Category: Scientific Session 12: Immunopathogenesis and antigen-specific thera

D. Wraith1, J. Chataway2, ATX-MS1467 Study Group

1Immunology & Immunotherapy | Medical & Dental Sciences, University of Birmingham, Birmingham, 2University College London (UCL) Institute of Neurology, London, United Kingdom

Autoimmune conditions can be treated by tolerance induction with peptide epitopes; this presentation will focus on the mechanisms involved and results from clinical trials of antigen-specific immunotherapy in multiple sclerosis. Peptides are designed as antigen processing independent epitopes (Apitopes) that mimic naturally processed antigens. Apitope induced peripheral tolerance is characterised by the generation of anergic, IL-10 secreting CD4+ T-cells with regulatory function. Clinical trials have tested the tolerability and efficacy of the peptide cocktail ATX-MS-1467 in participants with relapsing multiple sclerosis (RMS). Study 1 was a multicentre Phase 1b safety evaluation comparing intradermal (i.d., Cohort 1) with subcutaneous (Cohort 2) administration in 43 participants. Both cohorts received ATX-MS-1467 dosed at 25, 50, 100, 400, and 800 µg at 14-day intervals over 8 weeks, followed by 8 weeks with 4 additional 800 µg doses at 14-day intervals and 32 weeks off study medication. Study 2 was a Phase 2a, multicentre, single-arm, trial enrolling 37 participants. ATX-MS-1467 was titrated from 50 µg i.d. on Day 1 to 200 µg on Day 15 and 800 µg on Day 29 followed by biweekly administration of 800 µg for 16 weeks and 16 weeks off study medication. Efficacy was evaluated on MRI parameters and clinical variables. Safety end points included treatment-emergent adverse events and injection-site reactions. In Study 1 there was a significant decrease in new/persisting T1 GdE lesions in Cohort 1 from baseline to Week 16, returning to baseline values at week 48. In Study 2, the number of T1 GdE lesions were significantly reduced on treatment and remained reduced at study completion. Safety results were unremarkable in both studies. Based on these results we conclude that relatively slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions and a sustained effect post-treatment.
Disclosure: DW serves as Chief Scientific Officer for Apitope Technology (Bristol) Ltd and Apitope International NV on a consultative basis.

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